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Lysine crotonylation (Kcr) is an important post-translational modification, which is present in both histone and non-histone proteins, and plays a key role in a variety of biological processes such as metabolism and cell differentiation. Therefore, rapid and accurate identification of this modification has become a key task to study its biological effects. In the past few years, some calculation methods have been developed, but there is room for improvement in prediction performance. In this paper, we propose an effective model named DeepMM-Kcr, which is based on multiple features and an innovative deep learning framework. Multiple features are extracted from natural language processing features and hand-crafted features, where natural language processing features include token embedding and positional embedding encoded by transformer, and hand-crafted features include one-hot, amino acid index and position-weighted amino acid composition, and encoded by bidirectional long short-term memory network. Then natural language processing features and hand-crafted features are fusing by multi-head self-attention mechanism. Finally, a deep learning framework is constructed based on convolutional neural network, bidirectional gated recurrent unit and multilayer perceptron for robust prediction of Kcr sites. On the independent test set, the accuracy of DeepMM-Kcr is highest among the existing models. The experimental results show that our model has very good performance in predicting Kcr sites. The source datasets and codes (in Python) are publicly available at https://github.com/yunyunliang88/DeepMM-Kcr .

For advanced aircraft, the temperature environment inside the cabin is very severe due to the high flight speed and the compact concentration of the electronic equipment in the cabin. Accurately predicting the temperature environment induced inside the cabin during the flight of the aircraft can determine the temperature environment requirements of the onboard equipment inside the cabin and provide an accurate input for the thermal design optimization and test verification of the equipment. The temperature environment of the whole aircraft is divided into zones by the cluster analysis method; the heat transfer mechanism of the aircraft cabin is analyzed for the target area; and the influence of internal and external factors on the thermal environment is considered to establish the temperature environment prediction model of the target cabin. The coefficients of the equations in the model are parameterized to extract the long-term stable terms and trend change terms; with the help of the measured data of the flight state, the model coefficients are determined by a stepwise regression method; and the temperature value inside the aircraft cabin is the output by inputting parameters such as flight altitude, flight speed, and external temperature. The model validation results show that the established temperature environment prediction model can accurately predict the change curve of the cabin temperature during the flight of the aircraft, and the model has a good follow-up performance, which reduces the prediction error caused by the temperature hysteresis effect. For an aircraft, the estimated error is 2.8 °C at a confidence level of 95%. Engineering cases show that the application of this method can increase the thermal design requirements of the airborne equipment by 15 °C, increase the low-temperature test conditions by 17 °C, and avoid the problems caused by an insufficient design and over-testing. This method can accurately predict the internal temperature distribution of the cabin during the flight state of the aircraft, help designers determine the thermal design requirements of the airborne equipment, modify the thermal design and temperature test profile, and improve the environmental worth of the equipment.

A phase change materials (PCM)-based heat sink is an effective way to cool intermittent high-power electronic devices in aerospace applications such as airborne electronics and aircraft external carry. Optimizing the heat sink is significant in designing a compact and efficient system. This paper proposes an optimization procedure for the PCM/expanded graphite (EG)-based heat sink to minimize the temperature of the heat source. The numerical model is built to estimate the thermal response, and a surrogate model is fitted using the Kriging model. An optimization algorithm is constructed to predict the optimum parameters of the heat sink, and the effects of heat sink volume, heat flux, and working time on the optimal parameters of the heat sink are investigated. This shows that the numerical results agree well with the experimental data, and the proposed optimization method effectively obtains the optimal EG mass fraction and the geometric dimensions of the PCM enclosure. The optimal EG mass fraction increases with the rise in heat sink volume and decreases with the increase in heat flux and working time. The optimal ratio of the height to the length of the heat sink is 0.43. This study provides practical guidance for the optimal design of a PCM/EG-based heat sink.

Acetaminophen (APAP) is the major cause of drug-induced liver injury, with limited treatment options. APAP overdose invokes excessive oxidative stress that triggers mitochondria-to-nucleus retrograde pathways, contributing to APAP-induced liver injury (AILI). Mesenchymal stem cell therapy is a promising tool for acute liver failure. Therefore, the purpose of this study was to investigate the beneficial effects of adipose-derived mesenchymal stem cell (AMSC) therapy on AILI and reveal the potential therapeutic mechanisms. C57BL/6 mice were used as the animal model and AML12 normal murine hepatocytes as the cellular model of APAP overdose. Immunohistochemical staining, Western blotting, immunofluorescence staining, and RNA sequencing assays were used for assessing the efficacy and validating mechanisms of AMSC therapy. We found AMSC therapy effectively ameliorated AILI, while delayed AMSC injection lost its efficacy related to the c-Jun N-terminal kinase (JNK)-mediated mitochondrial retrograde pathways. We further found that AMSC therapy inhibited JNK activation and mitochondrial translocation, reducing APAP-induced mitochondrial damage. The downregulation of activated ataxia telangiectasia-mutated (ATM) and DNA damage response proteins in AMSC-treated mouse liver indicated AMSCs blocked the JNK-ATM pathway. Overall, AMSCs may be an effective treatment for AILI by inhibiting the JNK-ATM mitochondrial retrograde pathway, which improves APAP-induced mitochondrial dysfunction and liver injury.

Background Urinary tract infections (UTIs) are one of the most common infectious diseases worldwide, predominantly caused by Escherichia coli. We constructed a reporter phage T4::Nluc to achieve rapid, sensitive, and specific detection of Escherichia coli in UTIs. Methods T4::Nluc was constructed using the CRISPR/Cas9 system combined with homologous recombination and was confirmed through Sanger sequencing. The biological properties of T4 and T4::Nluc were compared. Time‐luminescence curves were detected to investigate the limit of detection (LOD) and the influence of urine. Additionally, the specificity of T4::Nluc was examined by co‐culturing it with other pathogens. In total, 104 urinary Escherichia coli isolates were collected to assess detection coverage. Finally, 698 urine samples were collected for clinical validation. Results T4::Nluc was confirmed to be correct. The one‐step growth curves of T4 and T4::Nluc were similar, but the optimal multiplicity of infection for T4 was 1, and that for T4::Nluc was 0.1, indicating that genetic modification had some effect. The LOD was 104 colony‐forming unit/mL detected at 220 min. Urine did not affect detection and T4::Nluc did not cross‐react with other pathogens. T4::Nluc could detect 38.46% of clinical strains, demonstrating higher sensitivity than the double‐layer overlay assay (25.96%). In clinical urine samples, its detection sensitivity was 36.59%, and the specificity was 100%. Conclusion T4::Nluc was successfully constructed and could detect Escherichia coli with superior sensitivity and specificity compared with traditional diagnostics, fulfilling the diagnostic criteria for UTIs while significantly reducing the detection time. This presented a novel approach for rapid and accurate detection of E. coli in UTIs. A reporter phage T4::Nluc was constructed using the CRISPR/Cas9 system combined with homologous recombination and was applied for the detection of clinical Escherichia coli in urinary tract infections (UTIs). T4::Nluc exhibited superior sensitivity and specificity, and had a short detection time, making it a powerful tool for diagnosing UTIs.

δ-opioid receptor (DOR) activation reduced brain ischemic infarction and attenuated neurological deficits, while DOR inhibition aggravated the ischemic damage. The underlying mechanisms are, however, not well understood yet. In this work, we asked if DOR activation protects the brain against ischemic injury through a brain-derived neurotrophic factor (BDNF) -TrkB pathway. We exposed adult male Sprague-Dawley rats to focal cerebral ischemia, which was induced by middle cerebral artery occlusion (MCAO). DOR agonist TAN-67 (60 nmol), antagonist Naltrindole (100 nmol) or artificial cerebral spinal fluid was injected into the lateral cerebroventricle 30 min before MCAO. Besides the detection of ischemic injury, the expression of BDNF, full-length and truncated TrkB, total CREB, p-CREB, p-ATF and CD11b was detected by Western blot and fluorescence immunostaining. DOR activation with TAN-67 significantly reduced the ischemic volume and largely reversed the decrease in full-length TrkB protein expression in the ischemic cortex and striatum without any appreciable change in cerebral blood flow, while the DOR antagonist Naltrindole aggregated the ischemic injury. However, the level of BDNF remained unchanged in the cortex, striatum and hippocampus at 24 hours after MCAO and did not change in response to DOR activation or inhibition. MCAO decreased both total CREB and pCREB in the striatum, but not in the cortex, while DOR inhibition promoted a further decrease in total and phosphorylated CREB in the striatum and decreased pATF-1 expression in the cortex. In addition, MCAO increased CD11b expression in the cortex, striatum and hippocampus, and DOR activation specifically attenuated the ischemic increase in the cortex but not in the striatum and hippocampus. DOR activation rescues TrkB signaling by reversing ischemia/reperfusion induced decrease in the full-length TrkB receptor and reduces brain injury in ischemia/reperfusion.

Mitochondria are vital for maintaining cellular homeostasis. However, mitochondrial damage is evident in patients with chronic hepatitis B (CHB). The role of mitochondrial dysfunction in the persistence of viral replication remains unclear. Therefore, this study aims to investigate the impact of mitochondrial dysfunction on HBV replication and elucidate the underlying mechanisms. Both mitochondria and lysosomes were dysfunctional in HBV-replicating cells. Moreover, HBV replication inhibited mitochondrial respiratory chain both and . Moderate inhibition of mitochondrial respiratory complex I activity using rotenone (Rot) increased HBV replication and decreased autophagic degradation capacity and . Mechanistically, elevated mitochondrial reactive oxygen species (mtROS) levels by Rot treatment or SOD2 knockdown led to deteriorated lysosomal membrane permeabilization, which elevated lysosomal pH and promoted HBV replication. Conversely, scavenging mtROS with mitoquinone (mitoQ) and mitoTEMPO (mitoT) had the opposite effect. Additionally, mitochondrial dysfunction reduced mitochondrial ATP production and diminished mitochondria-lysosome contacts. Obstructing mitochondrial ATP synthesis with Oligomycin A treatment or disruption of mitochondria-lysosome contacts with vacuolar protein sorting 13 A (VPS13A) knockdown resulted in lysosomal alkalinization and increased HBV replication by inhibiting vacuolar (H+)-adenosine triphosphatase (v-ATPase) assembly in an mtROS-independent manner. Ultimately, inhibition of mitochondrial complex I facilitated HBV secretion by promoting endosomal trafficking of HBV components. In conclusion, mitochondrial function plays a crucial role in HBV autophagic degradation. HBV impairs mitochondrial function, leading to a reduction in the lysosomal degradation capacity, which may hinder effective clearance of the virus.

Abstract Background/Aims: B and T lymphocyte attenuator (BTLA) is an immune inhibitory receptor involved in the pathogenesis of chronic viral infections. Little is known about the effects of BTLA gene polymorphisms on chronic hepatitis B virus (HBV) infections. In this study, we investigated whether the polymorphisms of BTLA are associated with the progression of chronic HBV infection. Methods: A total of 382 chronic HBV carriers and 170 healthy individuals in the same region were recruited for this study. The chronic HBV carriers were divided into three groups: asymptomatic HBV carriers (ASC), moderate chronic hepatitis B group (MCHB), and severe chronic hepatitis B group (SCHB). Two BTLA functional single nucleotide polymorphisms (SNPs; rs76844316 and rs9288952) were genotyped by polymerase chain reaction and sequenced directly. Results: The results showed that the frequency of the G allele of rs76844316 was significantly lower in the SCHB group than in the other three groups. Subjects bearing at least one G allele (TG or GG genotype) at rs76844316 had decreased susceptibility to severe chronic hepatitis B compared with those bearing the TT genotype. Haplotype analysis of the two SNPs revealed that the frequency of the G-G haplotype was significantly lower in SCHB patients than in controls. Moreover, in the SCHB group, patients carrying the G allele of rs76844316 tended to have lower ALT levels than those without it. Conclusion: Our findings suggest that the genetic variants of rs76844316 in BTLA influence the susceptibility to severe chronic hepatitis B and might play a protective role against the progression of chronic hepatitis B.

In this paper, a novel and compact magnetic field sensor based on the combination of an optical microfiber coupler interferometer (OMCI) and magnetic fluid (MF) is proposed. The sensor is made up of an OMCI cover with polydimethylsiloxane (PDMS) and MF, and it uses MF as a material for adjusting the magnetic refractive index and magnetic field response. The sensing characteristics of the sensor are analyzed, and the experimental test is carried out. Under the condition of the same OMC waist length, the sensor sensitivity increases with the decrease of the OMC waist radius. The sensitivity of 54.71 and 48.21 pm/Oe was obtained when the OMC waist radius was set at 3.5 and 4 μm, respectively. In addition, we also tested the sensing response time and vector response characteristics of the sensor. At the same time, we discuss the demodulation idea about the cross-sensitivity of the magnetic field and temperature. The sensor has the advantages of high sensitivity, low cost, small size, optimized performance, and convenient integration. It has huge application potential in the fields of navigation and industrial intelligent manufacturing.

Hepatitis B virus (HBV) can hijack the host bile acids (BAs) metabolic pathway during infection in cell and animal models. Additionally, microbiome was known to play critical role in the enterohepatic cycle of BAs. However, the impact of HBV infection and associated gut microbiota on the BA metabolism in chronic hepatitis B (CHB) patients is unknown. This study aimed to unveil the distinct BA profiles in chronic HBV infection (CHB) patients with no or mild hepatic injury, and to explore the relationship between HBV, microbiome and BA metabolism with clinical implications. Methods: Serum BA profiles were compared between CHB patients with normal ALT (CHB-NALT, n = 92), with abnormal ALT (CHB-AALT, n = 34) and healthy controls (HCs, n = 28) using UPLC-MS measurement. Hepatic gene expression in CHB patients were explored using previously published transcriptomic data. Fecal microbiome was compared between 30 CHB-NALT and 30 HCs using 16S rRNA sequencing, and key microbial function was predicted by PICRUSt analysis. Results: Significant higher percentage of conjugated BAs and primary BAs was found in CHB patients even without apparent liver injury. Combinatory BA features can discriminate CHB patients and HCs with high accuracy (AUC = 0.838). Up-regulation of BA importer Na+ taurocholate co-transporting peptide (NTCP) and down-regulation of bile salt export pump (BSEP) was found in CHB-NALT patients. The microbial diversity and abundance of Lactobacillus, Clostridium, Bifidobacterium were lower in CHB-NALT patients compared to healthy controls. Suppressed microbial bile salt hydrolases (BSH), 7-alpha-hydroxysteroid dehydrogenase (hdhA) and 3-dehydro-bile acid Delta 4, 6-reductase (BaiN) activity were found in CHB-NALT patients. Conclusion: This study provides new insight into the BA metabolism influenced both by HBV infection and associated gut microbiome modulations, and may lead to novel strategy for clinical management for chronic HBV infection.